Novel Mass Spectrometry-Based Approaches to Metabolite Profiling

presented by

Grace O'MailleThe Scripps Research Institute

September 22, 2005

The Scripps Research Institute, Tennis Court Room

Background:

Dr. O'Maille has been involved in scientific research for more than a decade. Starting in 1993, she was awarded a Howard Hughes summer fellowship to study microbiology and immunology in the laboratory of Prof. Richard D. Karp (at the University of Cincinnati). The following summer, she was awarded another research fellowship to investigate cellular transport and liposome function by employing various cell culture and molecular biology techniques in Prof. Ramund Pun's laboratory (at the University of Cincinnati). During her senior year as a Chemistry B.S. student, Dr. O'Maille conducted an undergraduate research project examining the biochemical properties of antibody binding properties in the laboratory of Prof. Pearl Tsang (Department of Chemistry at University of Cincinnati). Dr. O'Maille has received numerous distinctions, including the Achievement Award in Analytical Chemistry, Iota Sigma Pi Award, HyperChem Scholar, University Honors Award, and graduating Magnum Cum Laude. She is an active member in several professional societies, including Phi Beta Kappa National Honors Society, the American Chemical Society, and the Golden Key National Honors Society. She received her Ph. D. in Biochemistry from the laboratory of Prof. Gary Means at the Ohio State University in 2003. During her graduate work, Dr. O?Maille elucidated the kinetics of chemical modification of serum albumin by a variety of physiologically relevant small molecule drugs and effectors from human and related mammals. Dr. O'Maille is currently pursuing her interest in analytical biochemistry in the laboratory of Prof. Gary Siuzdak at Center for Mass Spectrometry of The Scripps Research Institute. Ongoing research is focused on human natural products identification, proteomic analysis of virus particles, and chemical modification of small molecules for ESI-LC-MS and GC-MS analyses. Several manuscripts are currently in press, under review, or in preparation.

Abstract:

The role of mass spectrometry in endogenous metabolite research is expanding largely due to technological improvements in ionization, mass accuracy and software. The primary challenge of ESI is that it is typically limited to relatively hydrophilic molecules. One approach to generating more comprehensive profiles is employing chemical derivatization. In this presentation, the utility of derivatization strategies combined with isotope labeling will be demonstrated for metabolite profiling in human serum. Two quantitative strategies have been employed to enhance ionization, and isotope labeling has been simultaneously used to improve quantitation. Results from studies on biomarker discovery in Sepsis will be presented.